title: Plasminogen activator inhibitor (PAI)-1 suppresses inhibition of gastric emptying by cholecystokinin (CCK) in mice.
abstract: The intestinal hormone cholecystokinin (CCK) delays gastric emptying and inhibits food intake by actions on vagal afferent neurons. Recent studies suggest plasminogen activator inhibitor (PAI)-1 suppresses the effect of CCK on food intake. In this study we asked whether PAI-1 also modulated CCK effects on gastric emptying. Five minute gastric emptying of liquid test meals was studied in conscious wild type mice (C57BL/6) and in transgenic mice over-expressing PAI-1 in gastric parietal cells (PAI-1H/Kβ mice), or null for PAI-1. The effects of exogenous PAI-1 and CCK8s on gastric emptying were studied after ip administration. Intragastric peptone delayed gastric emptying in C57BL/6 mice by a mechanism sensitive to the CCK-1 receptor antagonist lorglumide. Peptone did not delay gastric emptying in PAI-1-H/Kβ mice. Exogenous CCK delayed gastric emptying of a control test meal in C57BL/6 mice and this was attenuated by administration of PAI-1; exogenous CCK had no effect on emptying in PAI-1-H/Kβ mice. Prior administration of gastrin to increase gastric PAI-1 inhibited CCK-dependent effects on gastric emptying in C57BL/6 mice but not in PAI-1 null mice. Thus, both endogenous and exogenous PAI-1 inhibit the effects of CCK (whether exogenous or endogenous) on gastric emptying. The data are compatible with emerging evidence that gastric PAI-1 modulates vagal effects of CCK.
authors.affiliation: Physiological Laboratory, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: Joanne
authors.initials: J
authors.lastname: Gamble
authors.forename: Susan
authors.initials: S
authors.lastname: Kenny
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Dockray
mesh_terms: D000818:Animals; D002766:Cholecystokinin / Q000502:physiology*; D005746:Gastric Emptying; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017395:Plasminogen Activator Inhibitor 1 / Q000502:physiology*
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D002766:Cholecystokinin
keywords: CCK; G17; Gastric emptying; PAI; PAI-1; cholecystokinin; gastrin; plasminogen activator inhibitor